Population structuring of multi-copy, antigen-encoding genes in Plasmodium falciparum

Elife. 2012 Dec 18;1:e00093. doi: 10.7554/eLife.00093.

Abstract

The coexistence of multiple independently circulating strains in pathogen populations that undergo sexual recombination is a central question of epidemiology with profound implications for control. An agent-based model is developed that extends earlier 'strain theory' by addressing the var gene family of Plasmodium falciparum. The model explicitly considers the extensive diversity of multi-copy genes that undergo antigenic variation via sequential, mutually exclusive expression. It tracks the dynamics of all unique var repertoires in a population of hosts, and shows that even under high levels of sexual recombination, strain competition mediated through cross-immunity structures the parasite population into a subset of coexisting dominant repertoires of var genes whose degree of antigenic overlap depends on transmission intensity. Empirical comparison of patterns of genetic variation at antigenic and neutral sites supports this role for immune selection in structuring parasite diversity.DOI:http://dx.doi.org/10.7554/eLife.00093.001.

Keywords: Other; Plasmodium falciparum; antigenic diversity; epidemiological dynamics; immune selection; parasite population structure; var multi-gene family.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigenic Variation
  • Antigens, Protozoan / genetics*
  • Antigens, Protozoan / immunology
  • Child
  • Child, Preschool
  • Gene Expression Regulation
  • Genes, Protozoan*
  • Genetics, Population
  • Genome, Protozoan*
  • Host-Parasite Interactions
  • Humans
  • Infant
  • Infant, Newborn
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / parasitology
  • Middle Aged
  • Multigene Family
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / immunology
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / immunology

Substances

  • Antigens, Protozoan
  • Protozoan Proteins
  • erythrocyte membrane protein 1, Plasmodium falciparum